1. Field of the Invention
The present invention relates to sustained release pharmaceutical preparations and methods for producing the same. In particular, this invention relates to albuterol sulfate pharmaceutical sustained release formulations and their preparation.
2. Discussion of Background Information
Albuterol sulfate is a bronchodilator which is believed to be a beta-adrengenic agonist which stimulates beta-adrengeric receptor, which leads to relaxation of bronchial smooth muscle and inhibits hypersensitivity of mast cells. Albuterol sulfate is indicated for the relief of bronchospasm for the management of asthma and reversible obstructibe airway disease.
Albuterol sulfate is also known as, (±) ∝, -[(tert-butylamino)methyl]-4-hydroxy-m-xylene-∝,∝′-diol sulfate (2:1) salt, and has an empirical formula (C13H21NO3)2.H2SO4, a molecular weight of 576.7, and has the following structural formula:

Albuterol sulfate extended release tablets are currently available as Volmax® Tablets, which are available in two strengths, 4 and 8 mg, and manufactured by Glaxo Wellcome Ltd. UK England, Muro Pharmaceutical Inc., Tewksbury, Mass. The oral administration of Volmax® tablets provides a duration of action up to 12 hours, with the maximum concentration of drug in plasma being reached within 6 hours, and the plasma half-life being about 9 hours. Volmax® releases the drug from polymeric coated tablets through a laser drilled hole on one side of the tablet (OROS™ technology). The tablets include a rate controlling semi-permeable membrane, and a core of albuterol and osmotic agent. An osmotic gradient caused by core components draws water only into the tablet, where albuterol and osmotic agent dissolve, and albuterol is released through the laser drilled hole.
As disclosed in U.S. Pat. No. 5,837,379, the disclosure of which is incorporated by reference herein in its entirety, extended release tablets containing osmotic tablets are known which have had an osmotically active drug core surrounded by a semi-permeable membrane. As disclosed therein, the core can be divided into two layers, one containing the active drug and the other containing a push layer of pharmacologically inactive ingredients which are osmotically active in the presence of gastrointestinal fluids. Also, as disclosed therein, an outer water permeable coating provided with an aperture covers the tablet to allow the drug to be pushed out of the tablet. Products of this type are disclosed in U.S. Pat. Nos. 4,327,725, 4,612,008, 4,751,071, 4,765,989, 4,777,049, 4,783,337 and 4,851,229. The disclosures of which are each incorporated by reference herein in their entireties.
U.S. Pat. No. 4,503,030, the disclosure of which is incorporated by reference herein in its entirety, discloses an osmotic device for delivering drugs to the stomach and the intestine. The device disclosed therein includes a shaped wall around a compartment described as a compartment which maintains its physical and chemical integrity in the stomach but loses its chemical and physical integrity in the intestine.
U.S. Pat. No. 4,587,117, the disclosure of which is incorporated by reference herein in its entirety, discloses an oral osmotic device which has a shaped wall which loses its integrity at a pH of 3.5 to 8.0, a passageway from a compartment to the exterior of the device.
U.S. Pat. No. 5,837,379, the disclosure of which is incorporated by reference herein in its entirety, also discloses the belief that its osmotic tablet operates by water passing through the membrane on the surface of the tablet which causes the core to swell and increase the pressure inside the tablet. This is disclosed to cause a very slight expansion of the partially hydrated core which is controlled by the use of a relatively small amount of water swellable polymer. It is disclosed that the expansion of the core will cause the membrane to open to relieve the internal pressure, and that once the initial opening or openings are formed, the swelling effect of the core components will cause the contents of the core to extrude through the initial opening without complete disintegration of the membrane. It is further disclosed that the internal pressure which is exerted on the membrane by the swelling and expanding osmotic core is relieved by the passage of the first portions of the core contents through the initial openings.
Moreover, sustained release tablets are known, such as disclosed in U.S. Pat. Nos. 5,500,227, 6,024,982 and 6,210,714, the disclosures of which are each incorporated by reference herein in their entireties, wherein release of the drug is controlled by means of the resistance of a coating layer or matrix against the diffusion of the drug therethrough. The release of drugs from such formulations is disclosed to be driven, e.g., by the gradient of the drug concentration resulting from penetration of, e.g., gastric fluid, by diffusion into the formulation.
Still further, U.S. Pat. No. 6,245,351, the disclosure of which is incorporated by reference herein in its entirety, discloses a drug-containing core coated with a coating composition containing a water-insoluble substance and a swellable polymer having no basis groups.
U.S. Pat. No. 5,254,347, the disclosure of which is incorporated by reference herein in its entirety, discloses a controlled release pharmaceutical preparation, comprising a core containing a pharmaceutically active ingredient, and a porous film of a hydrophobic polymeric substance or a hydrophobic polymeric substance and a hydrophilic polymeric substance, the core being coated with the porous film. It is further disclosed that the hydrophobic polymeric substance may be ethyl cellulose and that the hydrophilic polymer may be a water-soluble polymeric substance such as methyl cellulose.
U.S. Pat. Nos. 5,674,895, 5,840,754, 5,912,268, 6,124,355 and 6,262,115, the disclosures of which are each incorporated by reference herein in their entireties, disclose a dosage form for delivering oxybutynin in a rate-controlled dose.